Cited by 868Neurotransmitter Receptor Influence on BehaviorStress Responses and CortisolSubstance Abuse Treatment and Outcomes

Stress dysregulation of drug reward pathways, and the transition to drug dependence

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Koob,, George, Kreek, Mary Jeanne·2007·American Journal of Psychiatry

Abstract

This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from limited access to drugs to long-term compulsive use of drugs. A dramatic escalation in drug intake with extended access to drug self-administration is characterized by a dysregulation of brain reward pathways. Hormonal studies using an experimenter-administered cocaine binge model and an escalation self-administration model have revealed large increases in ACTH and corticosterone in rats during an acute binge with attenuation during the chronic binge stage and a reactivation of the hypothalamic-pituitary-adrenal axis during acute withdrawal. The activation of the hypothalamic-pituitary-adrenal axis with cocaine appears to depend on feed-forward activation of the mesolimbic dopamine system. At the same time, escalation in drug intake with either extended access or dependence-induction produces an activation of the brain stress system's corticotropin-releasing factor outside of the hypothalamus in the extended amygdala, which is particularly evident during acute withdrawal. A model of the role of different levels of hormonal/brain stress activation in addiction is presented that has heuristic value for understanding individual vulnerability to drug dependence and novel treatments for the disorder.

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Crossref · 10.1176/appi.ajp.2007.05030503

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  • Chronic nicotine exposure causes neuroadaptations that produce widespread changes in brain neurotransmission, promoting and sustaining tobacco use.

    “The neuroadaptations arising from chronic nicotine exposure cause widespread alterations in brain neurotransmission that promote and sustain the use of tobacco [21–24].”

    From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [21]

  • In drug addiction, CRF is primarily involved in withdrawal from drugs of abuse.

    “In drug addiction, CRF is primarily involved in withdrawal from drugs of abuse (Koob and Kreek 2007; Koob 2008).”

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Research works printed but not linked: 3

  1. [22]Koob GF. The neurobiology of self-regulation failure in addiction: an allostatic view (commentary on Khantzian, “Understanding addictive vulnerability: an evolving psychodynamic perspective”) Neuro-Psychoanal. 2003;5:35–39. [Google Scholar]
  2. [44]Markou A, Koob GF. Intracranial self-stimulation thresholds as a measure of reward. In: Sahgal A, editor. Behavioural Neuroscience: A Practical Approach. vol 2. Oxford, UK: IRL Press; 1993. pp. 93–115. [Google Scholar]
  3. [53]Roberts AJ, Heyser CJ, Cole M, Griffin P, Koob GF. Excessive ethanol drinking following a history of dependence: animal models of allostasis. Neuropsychopharmacology. 2000;22:581–594. doi: 10.1016/S0893-133X(99)00167-0. [DOI] [PubMed] [Google Scholar] · DOI

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Authors
Koob, & Kreek, M. J.
Affiliations
Scripps Research Institute (US)
Venue
American Journal of Psychiatry
Published
2007-08
Volume
164
Issue
8
Pages
1149-1159
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
OpenAlex
W2166133075
Cited by
868
References
85
Citations by year
2026: 7 · 2025: 19 · 2024: 16 · 2023: 25 · 2022: 31 · 2021: 38 · 2020: 91 · 2019: 43 · 2018: 53 · 2017: 44 · 2016: 42 · 2015: 43 · 2014: 56 · 2013: 62 · 2012: 72
FWCI
4.75
Type
journal article
Language
en
Open access
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism (R01AA008459, AA-06420, AA-08459, P50AA006420, R37AA008459, P60AA006420)
  • National Institute of Mental Health (MH076537, R01MH076537)
  • National Institute on Drug Abuse (DA-00049, DA04043, DA04398, P50DA005130, K05DA000049, DA 05130, P60DA005130, R01DA004398, R01DA004043)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, P01DK026741)
  • National Center for Research Resources (RR024143, UL1RR024143)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
drug addiction, stress, hypothalamic-pituitary-adrenal axis, mesolimbic dopamine system, corticotropin-releasing factor, extended amygdala, withdrawal, ACTH, corticosterone, reward pathways, individual susceptibility
MeSH terms
Animals, Brain, Corticotropin-Releasing Hormone, Disease Models, Animal, Electrodes, Implanted, Hydrocortisone, Hypothalamus, Models, Neurological, Prolactin, Reinforcement, Psychology, Reward, Self Administration, Illicit Drugs, Stress, Physiological, Behavior, Addictive, Substance-Related Disorders, Rats

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